Since it has been proposed that pyrroloquinoline quinone (PQQ) may be a novel vitamin, it has drawn attention (see, for example, Non-patent Document 1). PQQ exists in not only bacteria but also in molds and yeasts, which are eukaryotes, and plays important roles as a coenzyme. Further, PQQ has so far been known to have a number of bioactivities such as the cell growth-promoting action, anti-cataract action, liver disease-preventing/curing action, wound-healing action, anti-allergic action, reverse transcriptase-inhibiting action, glyoxalase I-inhibiting action, carcinostatic action and nerve fiber-regenerating action.
PQQ can be produced by an organic chemical synthetic method (Non-patent Document 2), fermentation method (Patent Document 1) or the like. However, since PQQ obtained by these methods contains large amounts of water and impurities, a technology to obtain crystals of PQQ which are stable and highly pure has been demanded.
Crystals of a sodium salt of PQQ which were shown to be single crystal by X-ray crystallography have been obtained by evaporative concentration of the disodium salt of PQQ in phosphate buffer (Non-patent Document 3). However, this method is not suitable for mass production. Further, in a method by salting-out, since a salt used in a large amount, such as NaCl, is contaminated in the precipitated solids, there are drawbacks in that an operation of removal of the existing salt is required and that analysis for securing stable quality is difficult because of the salt.
As a method for obtaining crystals of PQQ having no such drawbacks, a method wherein a water-soluble organic solvent is added to cause recrystallization has been reported (Patent Document 2). However, there is no information on the crystal form in this literature, and, when the present inventors carried out a confirmatory experiment for recrystallization using ethanol, it was confirmed that the crystallinity of the disodium salt of PQQ was low and ethanol used as a solvent was likely to remain even after drying, so that it was difficult to provide crystals having stable quality. Further, the ethanol recrystallization method has a drawback in that the method requires a cooling apparatus for precipitating solids, which increases the cost of the process.
Further, in terms of the trisodium salt of PQQ, there has been no report on its crystal so far, unlike the disodium salt.